The Research Of Cognitive Impairment And Its Mechanism Induced By Intermittent Hypoxia In Rats

Objective:The injury model of rats with intermittent hypoxia was established to simulate the periodic "hypoxia-reoxygenation" model of OSAHS patients during sleep,and the correlation between cognitive function and behavior was tested to explore the correlation between them.Hippocampal tissue samples were taken for pathological examination and oxidative stress index determination,and the expression levels of Sesn2 and other related pathways and factors were detected in order to explore the expression and role of Sesn2 in cognitive impairment and brain oxidative stress injury induced by intermittent hypoxia and its possible mechanism.Methods:1.Ordinary SD rats were cultured in intermittent hypoxia environment,and the specific experimental conditions depended on the animal experimental device of intermittent hypoxia developed by ourselves.After 6 weeks,the general condition and blood oxygen saturation were detected,which proved the preliminary success of the model.2.The cognitive function of the modeled rats was tested and measured,including Morris water maze test,forced swimming test and open field test,and the results were compared.After completion,the hippocampal tissue was bluntly separated and preserved.3.The specimens were sliced and HE staining was used to observe the pathological changes and tissue injury.ELISA and staining electron microscope were used to determine the level of oxidative stress,and to determine the degree of oxidative stress injury and tissue damage in hippocampus.4.The antioxidant gene Sesn2,was selected to express only Sestrin2 protein.Western blotting(Western-Boltting)was used to detect the expression of Sestrin2 and the key proteins and pathway factors Nrf2 and mTOR,which may be closely related,to determine the change of Sesn2 expression level and possible expression signal pathway.Results:The animal experimental device of intermittent hypoxia developed and designed by ourselves runs well and the animal model is constructed successfully.Compared with the control group(NC group),the rats in the experimental group(IH group)ate less,their body weight increased slowly,and their blood oxygen saturation was significantly lower than that in the control group(NC group).The related cognitive function was impaired and the behavior was abnormal.HE staining showed that the injury of hippocampal tissue was serious,the level of oxidative stress was significantly increased,and the expression of antioxidant stress gene Sesn2 and important pathway proteins Nrf2 and mTOR were significantly increased.Conclusion:The intermittent hypoxia animal experimental device designed by ourselves plays a good supplement to the hypoxia-related animal experiments;intermittent hypoxia will affect the activity state,cognitive function and behavior of rats,and there is obvious oxidative stress damage in the hippocampus;the expression of related antioxidant stress genes such as Sesn2 is significantly increased and may be mediated and regulated by important proteins such as Nrf2 and mTOR.